Designing scaffolds with a capacity to load and deliver therapeutic molecules such as growth factors enhances tissue regeneration. Many strategies have been developed for this purpose, which involve the adsorption/binding of growth factors on the surface or their incorporation within the scaffolds. (Ziegler J et al., J Biomed Mater Rev, 2002, 59, 422-428; King W J et al., Adv Drug Deliv Rev, 2012, 64, 1239-1256; Yun Y R et at., J Tissue Eng. 2010, 1, 218142; Wenk E et al., Biomaterials, 2009, 30, 2571-2581).
Generally, the growth factors adsorbed on the surface present substantial initial burst effects owing to the weak electrostatic interactions. On the other hand, when the growth factors were incorporated within the scaffold's micro/nanostmcture, they could be better secured and undergo more sustained release. Scaffolding conditions, including pH, solvent type, temperature, and ionic strength are factors in the incorporation of growth factors. (Fransson J et al., I. Pharm Res, 1997, 14, 606-612; van de Weert M et. al., Pharm Res, 2000, 17, 1159-1167).
Possible scaffold design strategies that have been researched include securing growth factors within capsules/particles that are subsequently incorporated within scaffolds, covering or layering scaffolds to protect the incorporated growth factor, use of water-soluble compositions, and self-hardening/setting. (Whitaker M J et al., J Pharm Pharmacol, 2001, 53, 1427-1437; Mourino V et al., J R Soc Interface, 2010, 7, 209-227; Sokolsky-Papkov M et al., Adv Drug Deliv Rev, 2007, 59, 187-206).
Along with the issue of loading growth factors within scaffolds, the method of delivery is of special importance in achieving optimal biological functions. One promising strategy is the delivery of dual/multiple growth factors in a timely and sequential manner. One example is the effects of combined growth factors incorporated within scaffolds on bone formation, which produces an initial release of angiogenic growth factors including vascular endothelial growth factors (VEGFs) followed by the sequential release of osteogenic factors, such as bone morphoqenetic proteins (BMPs), which act to synergize bone formation through the scaffolds. (Kempen D H R et al., Biomaterials, 2009, 30, 2816-2825). Strategic methods to develop scaffolds with dual/multiple growth factor delivery potential have been recently proposed. (Patel Z S et al., Bone, 2008, 43, 931-940; Shah N J et al., Biomaterials, 2011, 32, 6183-6193; Young S et al., Tissue Eng A, 2009, 15, 2347-2362).
Under these circumstances, the inventors of the present invention added a calcium phosphate cement and a protein, drug or a combination thereof to an alginate solution in order to a prepare a core part composition and shell part composition each having different constitutions, and afterward inserted the above core part composition and shell part composition into the inner and outer nozzle of the concentric nozzle, respectively, subsequently injecting them into a calcium ion aqueous solution. Afterward, the above core part composition and shell part, composition were hardened, confirming that rapidly setting Alg/α-TCP scaffolds having core-shell structures that, are capable of controllably releasing a protein or drug can be prepared through this process, thereby completing the present invention.